c-, N- and L-Myc belong to a superfamily of related bHLH/LZ proteins and function in part as sequence-specific transcription factors involved in the regulation of genes controlling processes of cellular growth, differentiation and programmed cell death. Activities of Myc are highly dependent upon its dimerization with Max and are opposed by two other bHLH/LZ proteins, Mad and Mxi1. The contrasting biochemical properties of Myc and Mad or Mxi1 have led to a working model for the regulation of Myc- responsive genes in which transactivation-inert Mad or Mxi1 proteins compete with Myc for binding to both Max and to common target sequences. The goal of this proposal is to develop several biological systems for the elucidation of the functional interrelationships among members of the Myc superfamily and of how these interactions impact on the regulation of downstream effector genes.